Stochastic amplification and signaling in enzymatic futile cycles through noise-induced bistability with oscillations
Stochastic amplification and signaling in enzymatic futile cycles through noise-induced bistability with oscillations
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DOI：
10.1073/pnas.0406841102
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发表时间：
2005-02-15
影响因子：
11.1
通讯作者：
Arkin, AP
中科院分区：
文献类型：
--
作者：
Samoilov, M;Plyasunov, S;Arkin, AP
生物分子系统中的随机效应已经被认为是许多生物体发育和功能的重要生理和进化因素。然而，它们通常被认为只对经典确定性系统描述所预测的行为提供了适度的改进。在这项工作中，我们通过分析和数值研究表明，至少在一种普遍存在的（生物）化学反应机制中，酶的无效循环，外部噪声可能会诱导双稳态振荡（动态开关）行为，这种行为在数量和质量上都与预测或可能的确定性不同。我们进一步证明，产生这些不同特性所需的噪声本身可以由一组辅助化学反应引起，这使得足够复杂的生物系统可以在内部产生这种行为。然后，这种新的随机动力学为酶的无用循环机制赋予了额外的功能模式，包括随机放大和信号传导，其特征可以由驱动噪声的类型和参数控制。因此，这种由噪声引起的现象，除其他作用外，可能在包含这些循环和类似单元的通路中提供一种新型的控制机制。特别是，对调节网络中内源性或外部驱动的噪声诱导动力学的观察可能因此提供对其拓扑、结构和动力学的额外见解。
Stochastic effects in biomolecular systems have now been recognized as a major physiologically and evolutionarily important factor in the development and function of many living organisms. Nevertheless, they are often thought of as providing only moderate refinements to the behaviors otherwise predicted by the classical deterministic system description. in this work we show by using both analytical and numerical investigation that at least in one ubiquitous class of (bio)chemical-reaction mechanisms, enzymatic futile cycles, the external noise may induce a bistable oscillatory (dynamic switching) behavior that is both quantitatively and qualitatively different from what is predicted or possible deterministically. We further demonstrate that the noise required to produce these distinct properties can itself be caused by a set of auxiliary chemical reactions, making it feasible for biological systems of sufficient complexity to generate such behavior internally. This new stochastic dynamics then serves to confer additional functional modalities on the enzymatic futile cycle mechanism that include stochastic amplification and signaling, the characteristics of which could be controlled by both the type and parameters of the driving noise. Hence, such noise-induced phenomena may, among other roles, potentially offer a novel type of control mechanism in pathways that contain these cycles and the like units. In particular, observations of endogenous or externally driven noise-induced dynamics in regulatory networks may thus provide additional insight into their topology, structure, and kinetics.